World population continues to increase at a frightening rate, particularly in developing countries. Even at the very optimistic projection of 2.5 children per woman, global population will grow to over 15 billion by year 2100. In addition, approximately one-quarter of all pregnancies are unwanted, leading to millions of abortions (1.5 million surgical or medical abortions annually in the United States) and approximately 100,000 deaths worldwide per year of otherwise healthy young women due to the complications of abortion. It is well established that men will use contraceptives (approximately 30% of all contraception in the U.S. now is accomplished with male methods) and there are substantial problems with the safety and acceptability of existing female methods. Therefore, the development of new, effective, safe, reversible male contraceptives is an extremely important societal goal. The work proposed in this application is designed to increase our basic and clinical knowledge of reproductive processes in the male with particular relevance to contraception. We have five research projects: 1) oral testosterone for male hormonal contraception (Dr. J. Amory, P.I.), 2) spermatogonial stem cell self-renewal and differentiation (Dr. R. Braun, P.I.), 3) regulation of testis and sperm functions by cyclic nucleotide phosphodiesterases (Dr. J. Beavo, P.I.), 4) retinoic acid, Stra8, and key factors in the maturation of spermatogonia and the function of the testis (Dr. M. Griswold, P.I.) and 5) prostate and cardiovascular effects of male hormonal contraceptive regimens (Dr. W. Bremner, P.I.). We also propose a Program for Fellows and New Investigators in Male Contraception and an Administration Core Unit. Our application incorporates the talents of outstanding investigators of varied backgrounds and professional training into an interactive research program in reproductive biology. We have structured this Center to meld superb science with the practical goal of applying new basic knowledge as quickly as possible to studies in human beings. We hope that, in this way, our work will address critical needs of society.